DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway

A 2-Stage (Open-Label Followed by Randomized Double-Blind, Placebo-Controlled Stage), Phase 2 Trial of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor Pathway

The purpose of this study was to evaluate the safety and efficacy of once daily subcutaneous (SC) administration of setmelanotide in participants with obesity and specific gene variants in the MC4R pathway.

Key Inclusion Criteria:

• Participants must have had a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity
• Age 6 to 65 years, inclusive
• Obesity, defined as Body Mass Index (BMI) ≥40 kilograms per square meter (kg/m^2) for participants ≥18 years of age or BMI ≥97th percentile for age and gender for participants 6 to <18 years of age
• Study participant and/or parent or guardian were able to understand all study procedures and provide consent/assent
• Use of highly effective contraception
• Symptoms or behaviors of hyperphagia

Key Exclusion Criteria:

• Participants with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, Pro-opiomelanocortin (POMC), Proprotein convertase subtilisin/kexin type 1 (PCSK1), Leptin receptor (LEPR), nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 [SRC1]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that included the SH2B1 gene
• Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that had resulted in weight loss >2% within previous 3 months
• Bariatric surgery within the previous 6 months
• Documented diagnosis of current unstable major psychiatric disorder or a documented worsening of psychiatric condition that required changes in treatment within 2 years
• Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or Patient Health Questionnaire 9 (PHQ 9) score of ≥15 during Screening, any suicide attempt in participant's lifetime years, or any suicidal behavior in the last month.
• Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study
• Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity
• Glycated hemoglobin (HbA1C) >10.0% at Screening
• History of significant liver disease
• Glomerular filtration rate (GFR) <30 milliliter per minute (mL/min) at Screening
• History or close family history of melanoma or participant history of oculocutaneous albinism
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions
• Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
• Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
• Significant hypersensitivity to any excipient in the study drug
• Females who were breastfeeding or nursing

Other protocol defined Inclusion/Exclusion criteria applied.